It has been well known that certain peptides have physiological activities and their utilization has been studied extensively. Especially peptides bearing an acyl moiety at their N-terminal, viz, N-acyl peptides have shown interesting activity. Acid proteases, for example, have been reported to be specifically inhibited by N-acyl peptides, i.e., pepstatins, of the general formula: EQU R--Val--Val--X--Ala--X
wherein Val is L-valine, X is 4-amino-3-hydroxy-6-methyleptanoic acid or a salt or an ester thereof and Ala is L-alanine, and the carboxyl group of the X between Val and Ala being bound to the amino group of Ala to form a peptide bond and the amino group of the X between Val and Ala being bound to the carboxyl group of Val to form a peptide bond respectively, the amino group of the other X being bound to the carboxyl group of Ala to form a peptide bond and the carboxyl group of the other X being free or esterified or bound to a cation to form a salt, and R is an acyl radical having carbon atoms of 2 to 8 or an acyl radical partially substituted by one or more hydroxyl groups or halogen atoms or a C-terminal of an esterified carboxyl group, and the amino group of the Val adjacent to X being bound to the carboxyl group of the other Val to form a peptide bond and the carboxyl group of the R being to the amino group of the other Val to form an amide bond. PA1 werein R' is an acyl radical having 1 to 16 carbon atoms or an acyl radical partially substituted by one or more hydroxyl groups or halogen atoms or a C-Terminal of an esterified carboxyl group and the carboxyl of the R' being bound to the amino group of Val to form an amide bond and is an acyl radical which is the same as or different from the R of the above R--Val--Val--X--Ala--X and Val, Ala and X are the same as previously defined
Some of these compounds are reportedly effective on gastric ulcers due to their anti-activity. Clinical studies to this effect have been published.
These N-acyl peptides are characterized by the presence of a novel amino acid, designated in the formula as X, which is thought to be closely related to their physiological activity. The length of the peptide chain and the character of the acyl group are also related to the activity of these peptides.
It is possible to presume that if a peptide bearing X but no acyl group, having a shorter peptide chain length and still maintaining the protease inhibitory activity can be obtained, it will exhibit more varied actions and be able to be widely utilied, because its physiochemical and biological properties such as solubility, absorption and distribution in various organs will be different.